TAY SACHS AND ASHKENAZI JEWS – THE MYSTERY REVEALED:

Tay Sachs disease (TSD) is a rare genetic disorder due to some mutations on a particular gene called the HEXA gene located in the chromosome 15. The main reason as to why this disease doesn’t spread rapidly to the descendents is because it is an autosomal recessive disorder. There is only a 25% chance for the child of parents carrying copies of faulty HEXA genes to acquire the disease. However, Tay Sachs diseases is a fatal disorder characterized by deterioration of the neurons and subsequently due to the accumulation of a particular substance called GM2 gangliosides which is a type of lipid found in neurons. Due to the defective copies of the HEXA genes, the body mechanism fails to synthesize the active form of Hexosaminidase A enzyme which is responsible for the degradation of gangliosides.

There are variants of Tay Sachs Disease which are classified based on the time of onset of the disease. They are Infantile TSD, Juvenile TSD and Late Onset TSD. The infantile form of TSD is very fatal causing severe deterioration of the nerves and resulting in death of the infant by the age of 4. The juvenile form sets in between the age of 2 and 10 which is characterized by loss of cognitive and motor functions of the nerves and also results in death by the age of 15. The Late Onset TSD however is not fatal and is characterized by ataxia, psychiatric illness and neural deterioration.

The HEXA gene can be affected by over 100 different types of mutations which cause an alteration in the reading frame of the DNA resulting in a faulty enzyme. Tay Sachs disease is highly common among certain populations in the world due to continued inheritance and hybridization of a particular genetic defect described as 1278insTATC which is caused by the insertion of a base pair in exon 11 of the messenger RNA sequence. This means that an extra nucleotide has been added to the DNA sequence which transcribes and translates in the Hexosaminidase A enzyme. This totally alters the reading frame of the RNA sequence and therefore codes for different amino acids at key sites. The final product of the mutated DNA can no longer retain the functionality of the correct form of the enzyme.

This was one of the first mutations detected in a population based in Central and Eastern Europe called the Ashkenazi Jewish Population. This particular population is highly susceptible to other peculiar genetic disorders like Canavan Disease, Faconi Anemia, Cystic Fibrosis, Gauchers Disease and many more. The frequency of occurrence of TSD in Ashkenazi Jews is a startling 1 out of 30 individuals worldwide. The common form of TSD which usually affects these people is the infantile form of TSD. A major reason for the spread of this disease within the community is their rigid marital traditions and practices and also lack of awareness about the dangers of genetically inherited diseases.

However, the number of carriers of the disease is greater than the number actually affected by TSD, because the disease is not expressed in individuals possessing heterozygous alleles of HEXA gene containing one functional copy and one defective copy. So, it is very important to prevent the further spreading of the mutation among unaffected populations by efficient preventive techniques. With the advent in medical technology, it is possible to determine the genetic make-up of an individual by sampling a living tissue of the patient using techniques like PCR or ELISA to identify faulty genes or test the activity of Hexosaminidase enzymes. It is also possible to detect TSD early on in foetuses by carrying out amniocentesis or sampling of chorionic villi.